Precision Dosing of Alemtuzumab

NCT ID: NCT03302754

Last Updated: 2019-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-05
• Study Completion Date: 2019-03-10

Brief Summary

The purpose of this study is to conduct a pilot trial of a Precision Dosing approach to alemtuzumab dosing for allogeneic hematopoietic cell transplantation of patients with non-malignant diseases. The investigators will measure the ability to use a population PK model of alemtuzumab to target patient Day 0 alemtuzumab levels to 0.15-0.6ug/mL in a pilot study of 20 patients.

Detailed Description

The hypothesis is that the model-informed dosing regimen will prospectively allow the precision dosing of alemtuzumab to target Day 0 levels to fall between 0.15-0.6ug/mL in greater than 80% of patients. The investigators have chosen a conservative pilot study approach, and the aim is to achieve Day 0 alemtuzumab levels between 0.15-0.6ug/mL in greater than 60% of 20 patients enrolled in this pilot study based on a Simon two-stage design as detailed below.

A Simon two-stage design (Simon, 1989) is being used. The null hypothesis that 30% of patients will achieve a Day 0 alemtuzumab level between 0.15-0.6ug/mL will be tested against a one-sided alternative that the alemtuzumab dose modification will result in 60% of patients achieving a Day 0 alemtuzumab level between 0.15-0.6ug/mL. In the first stage, 7 patients will be accrued. If there are 2 or fewer patients that achieve Day 0 alemtuzumab levels within the range of 0.15-0.6ug/mL, the study will be stopped. Otherwise, 13 additional patients will be accrued for a total of 20. The null hypothesis will be rejected if 11 or more patients achieve a Day 0 level of 0.15-0.6ug/mL within the total 20 patients. This design yields a type I error rate of 0.04 and power of 0.82 when the true response rate is 0.60. The investigators will enroll up to 30 patients in order allow for subject withdrawal, but will stop enrollment once 20 patients reach Day 0.

Conditions

Allogeneic Hematopoietic Cell Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Alemtuzumab

Patients less than 15kg will be given 0.6mg/kg alemtuzumab divided over days -14, -13, and -12 (0.2mg/kg/dose).

Patients greater than 15kg will be given a 3mg "test" dose on day -14 in order to limit the first dose to no more than 3 mg per the manufacturer's recommendation. This will be followed by 0.23mg/kg/dose on days -13 and -12 (to equal a total dose of approximately 0.5-0.6mg/kg).

Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.

Group Type: OTHER

Alemtuzumab

Intervention Type: DRUG

Alemtuzumab (Campath®) is a recombinant DNA-derived humanized monoclonal antibody directed against CD52. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Alemtuzumab is a sterile, clear, colorless, isotonic pH 6.8-7.4 solution for injection. Alemtuzumab is supplied in single-use clear glass ampules containing 30 mg of Alemtuzumab in 3 mL of solution. Single use vial of alemtuzumab contains 30 mg alemtuzumab, 8 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate.

Interventions

Alemtuzumab

Alemtuzumab (Campath®) is a recombinant DNA-derived humanized monoclonal antibody directed against CD52. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Alemtuzumab is a sterile, clear, colorless, isotonic pH 6.8-7.4 solution for injection. Alemtuzumab is supplied in single-use clear glass ampules containing 30 mg of Alemtuzumab in 3 mL of solution. Single use vial of alemtuzumab contains 30 mg alemtuzumab, 8 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate.

Intervention Type: DRUG

Other Intervention Names

Campath

Eligibility Criteria

Inclusion Criteria

1. Patients who are undergoing RIC HCT with alemtuzumab, fludarabine, and melphalan at CCHMC for treatment of a non-malignant disease.

2. Age ≥ 6 weeks to ≤ 30 years (at time of enrollment).

3. For the first 7 patients, patients must have a 10/10 HLA matched related or unrelated stem cell donor, or be receiving a CD34+ selected stem cell product. After the first 7 patients, any donor match may be allowed after data review by the PI and medical monitor.

Exclusion Criteria

1. Patients with a history of anaphylaxis to alemtuzumab.

2. Patients who have previously received alemtuzumab and have not cleared alemtuzumab prior to the start of the preparative regimen.

3. Life expectancy less than 2 weeks.

4. Patients receiving dialysis.

5. Failure to sign informed consent and/or assent, or inability to undergo informed consent process.

6. It is not medically advisable to obtain the specimens necessary for this study.

7. Not able to tolerate subcutaneous dosing (patients with severe skin conditions such as epidermolysis bullosa).

• Minimum Eligible Age: 6 Weeks
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rebecca Marsh, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

2017-2206

Identifier Type: -

Identifier Source: org_study_id